Identification of the Fusion Peptide of Primate Immunodeficiency Viruses

Abstract

Membrane fusion induced by the envelope glycoproteins of human and simian immunodeficiency viruses (HIV and SIVmac) is a necessary step for the infection of CD4 cells and for the formation of syncytia after infection. Identification of the region in these molecules that mediates the fusion events is important for understanding and possibly interfering with HIV/SIVmac infection and pathogenesis. Amino acid substitutions were made in the 15 NH2-terminal residues of the SIVmac gp32 transmembrane glycoprotein, and the mutants were expressed in recombinant vaccinia viruses, which were then used to infect CD4-expressing T cell lines. Mutations that increased the overall hydrophobicity of the gp32 NH2-terminus increased the ability of the viral envelope to induce syncytia formation, whereas introduction of polar or charged amino acids in the same region abolished the fusogenic function of the viral envelope. Hydrophobicity in the NH2-terminal region of gp32 may therefore be an important correlate of viral virulence in vivo and could perhaps be exploited to generate a more effective animal model for the study of acquired immunodeficiency syndrome.

Fusion activity of flaviviruses: comparison of mature and immature (prM-containing) tick-borne encephalitis virions

“…In the case of myxo-, paramyxo-and retroviruses, a highly conserved hydrophobic sequence is liberated at or near the amino terminus of the membrane-associated part of the cleaved proteins (Bosch et al, 1989;Gallaher, 1987;Morrison, 1988;Wharton, 1987). Depending on the virus, this structural element is thought to trigger fusion activity either at physiological pH or after acid pH-induced conformational changes of the protein (Marsh & Helenius, 1989).…”

Comparison of lipid vesicle fusion induced by the putative fusion peptide of fertilin (a protein active in sperm‐egg fusion) and the NH2‐terminal domain of the HIV2 gp41

“…Studies on the molecular mechanism of viral fusion have allowed identification and characterization of a specific fusion protein [1]. One of the main characteristics of most viral fusion proteins is the presence of a relatively hydrophobic amino acid stretch, often referred as 'fusion peptide'.…”

Membrane-Transferring Regions of gp41 as Targets for HIV-1 Fusion Inhibition and Viral Neutralization

“…MTR membrane-activity is dependent on the adoption of structurally defined oligomeric complexes at membrane surfaces, a requirement that might explain, at least in part, their high degree of sequence conservation [19,[30][31][32]. Mutagenesis studies have put forward the absolute requirement of the FP sequence for gp41 fusogenic activity [49][50][51]. Amino acid homology between fusion proteins of different viruses is usually of less than 20%.…”